Few single institutions can meet the differing training needs of all types of clinical and translational (C&T) (T1- T4) investigators. The University of Texas Health Science Center at Houston (UTHSC-H) and the UT MD Anderson Cancer Center (UT MDACC) have a unique partnership with overlapping strengths and close proximity that allow us to meet these needs. Most T1-2 training is provided at UT MDACC and our joint Graduate School of Biomedical Sciences. T2-T4 research is based at UTHSC-H McGovern Medical School in collaboration with our Schools of Public Health, Biomedical informatics, Nursing, and Dentistry. We are applying for a CTSA to fund 6 KL2 Scholars per yr. To maximize the number and achievements of the C&T investigators trained by our hub, we will leverage CTSA funding to also support 6 Institutional Scholars per yr and enhance our program developing skilled C&T investigators throughout the immense Texas Medical Center (TMC) (9200 beds and 10 million encounters per yr) serving an extremely diverse patient population. Our Program includes: 1) the Clinical and Translational Research Curriculum (510 participants in past 5 yrs; 11 basic courses/workshops required for Scholars); 2) MS Courses & Degree in Clinical Research (65 TMC faculty & fellows in the past 5 yrs; optional for Scholars & tailored to an career development plan); and 3) the central focus of our Core: an Intensive Mentorship Program, (28 KL2 or Institutional Scholars & 27 other talented C&T investigators in past 5 yrs) that has been highly successful in helping mentees from our institutions, Baylor College of Medicine, and elsewhere to secure major grants, publish in high impact journals (NEJM, JAMA, and others), and become institutional and national academic leaders. Special strengths include our Scholars? research success involving multidisciplinary teams and other CTSA centers; improving the delivery, safety, and effectiveness of healthcare for pregnant women, children, and disadvantaged patients of any age; advancing the methods of C&T research using n-of-1 trials, Bayesian methods, and economic analyses; and showing reduced health system costs to secure adequate reimbursements to sustain and expand improved approaches to care delivery. Innovations in the next cycle will augment these strengths, enhance T1 research training, team science research, and interaction with industry, and promote learning health care (LHC) research through a novel LHC consultation service, a continuous community engagement program, and a special IRB panel to facilitate and advance the science and ethics of comparative effectiveness research, trials of emergency therapies, and implementation/de-implementation research. These and other Core features will promote the career development of Scholars within a LHC system to most rapidly advance clinical care and the health of diverse populations. With these innovations and our track record, infrastructure, and institutional support, CTSA funding will predictably produce a large return by developing innovative, collaborative, rigorous, and productive C&T investigators.